ArticleMolecular biology of the cell2012
An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 69 citations in OpenAlex.
- Trial
- PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2.Communications biology · 2026Article
- Immune-mediated strategies to solving the HIV reservoir problem.Nature reviews. Immunology · 2025Review
- Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.Current issues in molecular biology · 2025Review
- SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2.Journal of cell science · 2024Article
- CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- HIV-1 release requires Nef-induced caspase activation.PloS one · 2023Article
- Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers.International journal of molecular sciences · 2022Article
- Functional genomic analysis delineates regulatory mechanisms of GWAS-identified bipolar disorder risk variants.Genome medicine · 2022Article
- HIV-1 Nef-Induced Secretion of the Proinflammatory Protease TACE into Extracellular Vesicles Is Mediated by Raf-1 and Can Be Suppressed by Clinical Protein Kinase Inhibitors.Journal of virology · 2021Article
- The Role of L-Selectin in HIV Infection.Frontiers in microbiology · 2021Review
- Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation.iScience · 2020Article
- HIV-1 Impairment via UBE3A and HIV-1 Nef Interactions Utilizing the Ubiquitin Proteasome System.Viruses · 2019Article
- The autophagy protein ATG9A promotes HIV-1 infectivity.Retrovirology · 2019Article
- Lovastatin Inhibits HIV-1-Induced MHC-I Downregulation by Targeting Nef-AP-1 Complex Formation: A New Strategy to Boost Immune Eradication of HIV-1 Infected Cells.Frontiers in immunology · 2019Article
- Article
- HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System.Journal of virology · 2018Article
- HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure.AIDS research and therapy · 2017Review
- Viral effects on the content and function of extracellular vesicles.Nature reviews. Microbiology · 2017Review
- Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization.Cell death and differentiation · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef directs virus escape from immune surveillance by subverting host cell intracellular signaling and membrane traffic to down-regulate cell-surface major histocompatibility complex class I (MHC-I). The interaction of Nef with the sorting proteins PACS-1 and PACS-2 mediates key signaling and trafficking steps required for Nef-mediated MHC-I down-regulation. Little is known, however, about the molecular basis underlying the Nef-PACS interaction. Here we identify the sites on Nef and the PACS proteins required for their interaction and describe the consequences of disrupting this interaction for Nef action. A previously unidentified cargo subsite on PACS-1 and PACS-2 interacted with a bipartite site on Nef formed by the EEEE(65) acidic cluster on the N-terminal domain and W(113) in the core domain. Mutation of these sites prevented the interaction between Nef and the PACS proteins on Rab5 (PACS-2 and PACS-1)- or Rab7 (PACS-1)-positive endosomes as determined by bimolecular fluorescence complementation and caused a Nef mutant defective in PACS binding to localize to distorted endosomal compartments. Consequently, disruption of the Nef-PACS interaction repressed Nef-induced MHC-I down-regulation in peripheral blood mononuclear cells. Our results provide insight into the molecular basis of Nef action and suggest new strategies to combat HIV-1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.